Esophageal adenocarcinoma [EAC] incidence has increased by at least four fold over the last three decades and is increasing by 1-2% annually. It is also one the most lethal cancers - as eighty percent of EAC patients die of their disease - most within 2 years of diagnosis. These dismal outcomes occur in spite improvements in surgical and endoscopic therapies. It is extremely unlikely that advances in cancer therapeutics - without progress in early detection and prevention - will have a significant impact on this high mortality rate in the near future. Barrett's Esophagus [BE], defined as intestinal metaplasia [IM] of the esophagus, is the only established precursor of EAC and is diagnosed via upper GI endoscopy [EGD] and biopsy. Due to high cost of EGD, screening even in patients with reflux is not routinely performed. Thus less than 5% of EACs are diagnosed in individuals with previously detected BE. Most BE remains undetected though it affects up to 7% of the population. We have identified a biomarker, aberrantly methylated vimentin [mVIM], which has greater than 90% sensitivity and specificity for BE in upper GI samples. The detection of this marker in upper GI tract samples is eminently feasible using current technologies. The UH2 portion will validate this marker on two platforms - methylation specific real time PCR and methylation specific NGS. This validation will occur at Case Medical Center with the support of the discoverers of mVIM at Case Western Reserve University [CWRU]. Laboratory validation will occur using established CLIA/CAP standards The UH3 portion will clinically validate the mVIM assay based on two clinical trials accessing esophageal cytology samples as a method for screening for BE. The trials will look at two patient groups: known BE patients vs. controls; and patients presenting with upper GI symptoms. A novel component of these trials is the use of a balloon device invented at CWRU for the purpose of obtaining samples of the distal esophagus without sedation and with minimal discomfort. In pre-human testing the device gave x10 the DNA needed for the proposed assays. The combination of an easy to use, efficient esophageal sampling device and a CLIA approved Laboratory Developed Test offers a real chance to identify asymptomatic individuals with BE, allowing them an opportunity to be enrolled in BE surveillance programs before the onset of EAC. Based on initial testing the laboratory and clinical validations will have sensitivities and specificities sufficient to allow for follow-on stps leading to commercialization.